INTRODUCTION — Abnormal uterine bleeding (AUB) refers to uterine bleeding in a nonpregnant female that is abnormal in volume, frequency, duration, and/or regularity .
The evaluation of common causes of AUB in adolescents will be discussed here. The management of AUB in adolescents and a more comprehensive discussion of the evaluation of AUB in older reproductive-age females are presented separately.
●(See "Abnormal uterine bleeding in adolescents: Management".)
●(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis".)
NORMAL MENSTRUAL CYCLE IN ADOLESCENTS — The normal menstrual cycle results from a complex feedback system involving the hypothalamus, pituitary, ovary, and uterus (figure 1).
Timing and flow — Menstrual cycles vary considerably during the first few years after menarche given irregularities in ovulation. The majority of cycles in adolescents last 21 to 45 days with two to seven days of menstrual bleeding (figure 2) [2-5]. The average adult menstrual cycle lasts 28 days to 35 days with four to six days of menstrual bleeding. The median blood loss during each menstrual period is 30 mL; the upper limit of normal is 80 mL. (See "Normal menstrual cycle".)
In a systematic review of observational studies describing menstruation during the first year after menarche, the mean cycle length was 34.5 days (range 32 to 61) and decreased throughout the year . Mean bleeding duration ranged from 4.9 to 5.4 days; bleeding of ≥7 days' duration occurred in 2 to 11 percent of cycles.
Establishing ovulatory cycles — The duration of time that it takes to establish regular ovulatory cycles increases with increasing age at the time of menarche [6-8]. One-half of cycles are ovulatory by one year in females with menarche at <12 years, by three years in females with menarche between 12 and 13 years, and by 4.5 years in females with menarche at ≥13 years . (See 'Anovulatory uterine bleeding' below.)
In the first year or two after menarche, all adolescent females are prone to anovulatory cycles in which the endometrium lacks the stabilizing effect of progesterone. In such cycles, the endometrium becomes excessively thickened. It breaks down and sloughs when estrogen is withdrawn (estrogen-withdrawal bleeding) or when it becomes unstable (estrogen-breakthrough bleeding) .
Adolescents with regular menses have cyclic estrogen secretion that permits orderly growth and shedding of the endometrium (estrogen-withdrawal bleeding), even in the absence of ovulation. In addition, when ovulatory cycles do occur, they are associated with increased progesterone secretion, which helps to stabilize endometrial growth and permits more complete shedding .
Adolescents with irregular menses and anovulatory bleeding appear to have delayed maturation or dysfunction of the hypothalamic-pituitary-ovarian axis. In these adolescents, the midcycle surge of luteinizing hormone does not occur and estrogen secretion is sustained in the absence of progesterone [10,11]. The endometrium proliferates beyond the ability of estrogen to maintain it. Irregular, heavy bleeding occurs when the endometrium becomes unstable (estrogen-breakthrough bleeding) and continues until estrogen-induced repair takes place .
●AUB – AUB refers to menstrual bleeding that occurs outside the normal range, and includes [1,2,12]:
•Absence of menses (amenorrhea)
•Menses at irregular intervals
•For adolescents, menstrual periods more frequently than every 21 days or less frequently than every 45 days 
•Excessive in duration (ie, >7 days)
•Heavy menstrual bleeding, defined subjectively as a volume of menstrual flow that interferes with quality of life (physical, emotional, social, and/or material) [1,13]
•Intermenstrual or breakthrough bleeding
●Anovulatory uterine bleeding – "Anovulatory uterine bleeding" is the preferred term for heavy noncyclic uterine bleeding unrelated to structural lesions of the uterus, systemic disease, or sexually transmitted infection . This pattern of bleeding was previously called "dysfunctional uterine bleeding." In the FIGO classification system, anovulatory uterine bleeding is classified as a type of ovulatory dysfunction .
CAUSES OF VAGINAL BLEEDING IN ADOLESCENTS — Adolescents with AUB typically present with a complaint of abnormal "vaginal bleeding." The uterus is the most likely source of vaginal bleeding (table 1). Other sources include the ovary, cervix, vagina, vulva, gastrointestinal tract, and urinary tract. Nonuterine sources of vaginal bleeding are discussed separately. (See "Causes of female genital tract bleeding" and "Evaluation of vulvovaginal bleeding in children and adolescents".)
Heavy bleeding is typically from the uterus, whereas light bleeding, staining, or spotting may be from any site along the genital tract. Postcoital bleeding suggests bleeding from the cervix or other lower genital tract source. Bleeding that occurs solely with urination or defecation suggests a urinary or gastrointestinal source. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis", section on 'Gynecologic and obstetric history'.)
The most common cause of AUB in adolescents during the initial one to two years of menstruation are anovulatory cycles, which are related to immaturity of the hypothalamic-pituitary-ovarian axis [3,11,16]. Other common causes of AUB in adolescents include pregnancy/pregnancy-related problems, bleeding disorders (including bleeding related to systemic disease), polycystic ovary syndrome, thyroid dysfunction, hypothalamic dysfunction (eg, related to stress, exercise, underweight, acute weight loss, or obesity), hormonal or intrauterine contraception, and infection (table 1). More than one cause may contribute or exacerbate AUB in a given adolescent.
The underlying cause of AUB determines the treatment, which ranges from observation (eg, for mild anovulatory uterine bleeding) to pharmacologic (for moderate or severe anovulatory uterine bleeding) and/or surgical therapy (eg, for leiomyoma). (See "Abnormal uterine bleeding in adolescents: Management".)
Triage — Initial triage of the adolescent with suspected AUB includes assessment of hemodynamic stability and pregnancy status, which influence disposition, differential diagnosis, and further evaluation.
●Patients who are hemodynamically unstable (eg, tachycardic, hypotensive, orthostatic) should be referred/transported to the emergency department for stabilization and hospitalization before proceeding with additional evaluation.
Blood should be obtained for cross-matching in the event transfusion is necessary. Blood for evaluation of bleeding disorders should be obtained before administration of blood products or estrogen. (See 'Bleeding disorders' below and "Abnormal uterine bleeding in adolescents: Management", section on 'Additional evaluation'.)
●Patients who are hemodynamically stable can be further evaluated in the outpatient setting.
It is essential to obtain a urine pregnancy test in adolescents who present with unexplained vaginal bleeding, regardless of the stated sexual history; adolescents may be unwilling to disclose sexual activity for a variety of reasons. Pregnancy and pregnancy-related problems are a common cause of uterine bleeding in adolescents and may be life-threatening.
●If the urine pregnancy test is positive, the etiology of the bleeding should be evaluated with serum beta-hCG and/or ultrasonography. Vaginal bleeding with pregnancy may be a result of:
•Early pregnancy loss or second trimester pregnancy loss (see "Pregnancy loss (miscarriage): Terminology, risk factors, and etiology")
•Ectopic pregnancy (see "Ectopic pregnancy: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation')
•Molar pregnancy (see "Hydatidiform mole: Epidemiology, clinical features, and diagnosis", section on 'Diagnostic evaluation')
Additional causes of vaginal bleeding in pregnant patients are discussed separately. (See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)
●If the urine pregnancy test is negative, the patient is evaluated for nonpregnancy-related causes of AUB.
History — The history (table 2) should be obtained both with and without the patient's caregiver. The caregiver may be more precise about menstrual patterns and may share details that the patient would omit. In addition, adolescents may be more comfortable discussing menstruation if a caregiver is present. Speaking with the patient alone maintains their confidentiality on subjects that they may be uncomfortable discussing in front of their caregiver (eg, sexual activity). (See "Confidentiality in adolescent health care", section on 'Overview'.)
●Menstrual history – It is important to obtain as much information as possible about the menstrual history, including age of menarche, menstrual pattern, associated symptoms, and events that coincided with a change in the menstrual pattern (if there has been a change) (table 2) .
We ask patients with irregular cycles to maintain a menstrual calendar, either on paper (figure 3) or using a one of several freely available smart phone "apps" . We encourage all patients to track their periods  so they can prepare for the onset of menstrual symptoms and bleeding.
Heavy menstrual bleeding is defined clinically as bleeding that interferes with activities and/or physical, emotional, social, and/or material quality of life [1,13]. Although it is important to try to quantify the volume of menstrual blood flow in females who report heavy menstrual flow, neither patients nor clinicians can accurately estimate the volume of blood loss [18,19]. The large variety of menstrual products on the market makes quantification challenging at best. In addition, there is little correlation between the number of pads or tampons used and actual menstrual blood loss . In adolescents, hygiene preferences and school limitations can affect the quantity of sanitary products used. Nonetheless, the history should include the type/size of pad or tampon used, the number of pads or tampons used per day (or the hours each item is worn ), and an estimate of the degree to which the pad or tampon is soaked .
The pictorial blood loss assessment chart (PBAC) score is a semi-quantitative tool for measuring menstrual bleeding (figure 4). The PBAC score is calculated from the number of pads or tampons used, the degree to which each is saturated, and the passage of blood clots . A score of ≥100 has been correlated with heavy menstrual bleeding [23,24]. In an observational study, PBAC scores correlated with adolescents' self-report of "heavy," "medium" (normal), and "light" menstrual flow; additional studies are necessary to confirm the findings and determine the appropriate cutoff value for adolescents .
In the absence of other means to measure blood loss, the clinician must rely upon indirect indicators of heavy flow, such as passing blood clots larger than 2.5 cm (1 inch) in diameter, bleeding through clothes, the need to change sanitary protection during the night, signs or symptoms of volume depletion during the menstrual period, and measurement of hemoglobin or hematocrit (table 3) [26-28]. (See 'Laboratory evaluation' below.)
●Sexual history – The sexual history should be obtained without the caregiver present. History should include information regarding contraception and condom use; number of partners; new partners; history of sexually transmitted infections (STIs) or current symptoms (eg, vaginal discharge, pelvic pain, bleeding with intercourse); previous pregnancy or abortion; whether sexual activity was forced or consensual; and whether the adolescent has a history of sexual abuse or assault (table 2) [3,9,29]. (See "Screening for sexually transmitted infections", section on 'Sexual history'.)
●Past medical history – The past medical history should include information about (table 2) [3,11]:
•Systemic illness, including hematologic or renal disease, gastrointestinal bleeding
•Current or recent medications (including over-the-counter medications and complementary/alternative agents); ask specifically about:
-Contraceptive use and method (some forms may cause irregular bleeding)
-Nonsteroidal anti-inflammatory drugs, including aspirin, and aspirin-containing over-the-counter medications (anticoagulation effects); antiplatelet medications can precipitate bleeding that may not have occurred otherwise in patients with von Willebrand disease (see "Approach to the child with bleeding symptoms", section on 'Medications' and "Clinical presentation and diagnosis of von Willebrand disease", section on 'Clinical features')
-Valproic acid (anticoagulation effects)
-Antidepressants and antipsychotics (may affect the hypothalamic-pituitary-ovarian axis)
●Review of systems – The review of systems should include information about weight change (loss or gain), fatigue, self-induced vomiting as a means of weight control, disordered eating behaviors, hirsutism, acne, visual changes, headaches, galactorrhea, change in bowel habits, and abdominal pain (table 2) . Unexplained weight changes, palpitations, heat or cold intolerance, and/or changes in hair, skin, or nails may indicate thyroid dysfunction or malnutrition . Bleeding that occurs solely with urination or defecation suggests a urinary or gastrointestinal source.
Adolescent females with complaints of heavy menstrual flow should be asked about bleeding from other sites (easy bruising, epistaxis, gingival bleeding, postoperative bleeding) and symptoms of acute or chronic anemia (lightheadedness, fatigue, syncope, weakness, headache) [3,9,11,31].
●Social history – The social history should include information about social stressors, substance use, exercise patterns/athletic participation (eg, intensity of exercise and training). Asking questions about school absence or decreased participation in recreational activities (eg, sports, hobbies) related to menses may provide information about effects on quality of life .
●Family history – The family history should include information about bleeding disorders, infertility, menstrual disorders, thyroid disease, and leukemia or other types of cancer [3,32,33]. A strong family history of diabetes mellitus and or disorders of lipids or triglycerides may be suggestive of polycystic ovary syndrome (PCOS). (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents".)
Physical examination — Information from the physical examination may help to narrow the diagnostic possibilities and target subsequent laboratory or radiographic evaluation (table 4).
●General examination – The general examination should include (table 4) [3,11,32]:
•Measurement of height, weight, and arm span.
•Visual assessment of body habitus and fat distribution (eg, Cushing syndrome, Turner syndrome).
•Vital signs, including orthostatic vital signs.
•Palpation of the thyroid gland for enlargement or other abnormalities.
•Signs of androgen excess (eg, hirsutism, acne, male-pattern balding) to evaluate for PCOS. (See "Diagnostic evaluation of polycystic ovary syndrome in adolescents", section on 'History and physical examination'.)
•Evidence of easy bruising or oozing gums to evaluate for a bleeding disorder.
•Examination of the optic fundi and visual field testing to evaluate the possibility of a pituitary tumor.
•Assessment of lymph nodes (lymphadenopathy may be a sign of malignancy).
•Sexual maturity rating of the breasts (picture 1) and assessment for galactorrhea. Breast development provides evidence of estrogenization.
•Examination of the hair and skin for thinning hair, dry skin, excessive sweating, acanthosis nigricans, or signs of abnormal bleeding (eg, petechiae and/or bruising) should be noted, particularly in patients with heavy menstrual bleeding.
•Palpation of the abdomen (pregnancy, uterine mass, ovarian mass).
●External genitalia – Examination of external genitalia includes evaluation of clitoral size, sexual maturity rating for pubic hair development (picture 2), and the hymen (figure 5).
It is also important to look for extrauterine sources of bleeding (eg, perineal trauma, vulvar lesions, signs of STIs). Adolescent females who have signs of perineal trauma should be questioned privately about sexual abuse or assault. (See "Sexually transmitted infections: Issues specific to adolescents", section on 'STI clinical patterns' and "Evaluation of sexual abuse in children and adolescents".)
●Pelvic examination – Pelvic examination may be distressing for adolescent females, especially those who are not sexually active. Unless the bleeding is severe, the pelvic and rectal examination may be postponed pending a trial of medical therapy, if such therapy is warranted. As an alternative, pelvic ultrasonography can provide relevant information about genital tract anatomy. (See "Abnormal uterine bleeding in adolescents: Management" and "Congenital anomalies of the hymen and vagina".)
When warranted, many adolescents can tolerate a one finger digital examination (provided the hymenal opening is wide enough to admit the finger ) to assess the depth of the vagina and the presence and normality of the cervix, uterus, and ovaries. A rectoabdominal examination may be helpful if the digital examination is uncomfortable or not possible.
Many adolescents also can tolerate a speculum examination with an appropriate size speculum to look for abnormalities (eg, polyps, vaginal lacerations).
Pelvic examination under anesthesia may be necessary if pelvic examination is inadequate or an appropriate diagnosis cannot be established despite imaging.
Pelvic ultrasonography — Pelvic ultrasonography via the abdomen is another method of evaluating pelvic anatomy (ie, vagina, uterus, ovaries) in adolescents when clinicians prefer to avoid digital and/or speculum examination or when digital and/or speculum examinations are limited. Pelvic ultrasonography can also evaluate structural abnormalities (ie, vaginal or cervical outlet obstruction in patients with cyclic pain, fibroids, polyps, or ovarian masses).
Relevant findings on pelvic ultrasonography may include:
●Vaginal or cervical outlet obstruction in patients with cyclic pain (see "Congenital anomalies of the hymen and vagina" and "Benign cervical lesions and congenital anomalies of the cervix")
●Leiomyomas (fibroids) (see "Uterine fibroids (leiomyomas): Epidemiology, clinical features, diagnosis, and natural history", section on 'Diagnostic evaluation')
●Ovarian mass (see "Ovarian cysts in infants, children, and adolescents")
●Multiple follicles around the periphery of the ovary (may indicate PCOS) (see "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Differential diagnosis')
Laboratory evaluation — Our initial evaluation for adolescents who present with AUB generally includes:
●Pregnancy test (if not already performed)
●Hemoglobin or hematocrit with a platelet count
●Measurement of thyroid-stimulating hormone (TSH)
●Screening for STIs if sexually active (see "Screening for sexually transmitted infections", section on 'Females')
Prolactin measurement may also be warranted, particularly in females with headaches or nipple/breast complaints (eg, galactorrhea). (See "Clinical manifestations and evaluation of hyperprolactinemia", section on 'Clinical presentation'.)
Additional laboratory evaluation for adolescents with AUB depends upon the pattern of bleeding and findings from the history and examination. (See 'Causes of amenorrhea' below and 'Causes of irregular bleeding' below and 'Causes of heavy menstrual bleeding' below and 'Causes of intermenstrual bleeding' below.)
APPROACH TO DIAGNOSIS
Classify the bleeding pattern — Information from the initial evaluation is used to classify abnormal genital bleeding into one of the following patterns (table 5) :
●Amenorrhea (absence of menses)
●Irregular bleeding (unpredictable intervals between episodes of menstrual bleeding)
●Prolonged and/or heavy menstrual bleeding
•Prolonged menstrual bleeding lasts >7 days.
•Heavy menstrual bleeding is defined clinically as soaking a pad or tampon more than every two hours (figure 4) or interfering with activities and/or quality of life (physical, emotional, social, and/or material) [1,13]. (See 'History' above.)
●Intermenstrual bleeding (bleeding between well-defined cyclical menses) (figure 6)
Although this categorization narrows the differential diagnosis and determines the need for additional testing (table 5), it may be difficult to classify the abnormal menstrual bleeding into a particular pattern for a number of reasons. Menstrual cycles can vary substantially in the first year or two after menarche. The distinction between regular and irregular cycles is not always clear. The categories may overlap (eg, irregular bleeding can also be heavy). Causative conditions may have more than one pattern or present atypically.
Causes of amenorrhea — Amenorrhea is the absence of menses. Amenorrhea may be primary (absence of menarche by age 15 years) or secondary (absence of menses for ≥90 days in females who previously had regular menstrual cycles or >6 months in those who had irregular menses). Pregnancy is the most common cause of amenorrhea in reproductive-age females. (See "Pregnancy in adolescents", section on 'Diagnosis of pregnancy'.)
Other causes of amenorrhea and the evaluation and management of primary and secondary amenorrhea are discussed separately. (See "Causes of primary amenorrhea" and "Evaluation and management of primary amenorrhea" and "Epidemiology and causes of secondary amenorrhea" and "Evaluation and management of secondary amenorrhea".)
Causes of irregular bleeding — Irregular bleeding refers to unpredictable intervals between episodes of menstrual bleeding. Irregular bleeding also may be prolonged and/or heavy.
Anovulatory uterine bleeding — During the first one to two years after menarche, the most common cause of irregular bleeding in nonpregnant adolescents is anovulatory uterine bleeding due to an immature hypothalamic-pituitary-ovarian axis [3,16,35]. (See 'Establishing ovulatory cycles' above.)
Clinical features suggestive of anovulatory uterine bleeding include irregular periods and the absence of premenstrual symptoms (eg, breast tenderness, bloating, mood swings, or uterine cramping). The irregular bleeding pattern commonly is characterized by phases of two or more months without bleeding followed by phases with spotting, heavy bleeding, or sudden and substantial hemorrhage .
Although laboratory evaluation is not necessary to diagnose anovulation or immaturity of the hypothalamic-pituitary-ovarian axis in a patient with a typical clinical presentation, before attributing AUB to immaturity of the hypothalamic-pituitary-ovarian axis, other causes of ovulatory dysfunction in adolescents (table 1) must be considered and excluded.
The need for laboratory evaluation for other causes of anovulatory bleeding is determined by the findings in the history (table 2) and examination (table 4). In addition to the initial laboratory evaluation described above (see 'Laboratory evaluation' above), evaluation for other conditions of ovulatory dysfunction may include:
●Follicle-stimulating hormone (FSH) to evaluate the hypothalamic-pituitary-ovarian axis
An elevated FSH suggests ovarian insufficiency. When possible, we try to obtain FSH on day 3 of the menstrual cycle (by convention, the first day of menses is day 1 of the cycle, even in females with irregular cycles). Although the concentrations of FSH vary throughout the cycle (figure 1), they are most reproducible on day 3, when they are at their lowest concentrations. If day 3 is not reproducible because of the pattern of bleeding, FSH may be obtained at any time during the cycle. However, the concentration may not be at its nadir and repeat testing may be necessary to assess the accuracy of the result.
●Thyroid-stimulating hormone (TSH) to screen for hypothyroidism and hyperthyroidism, if not already performed (see "Acquired hypothyroidism in childhood and adolescence", section on 'Diagnosis' and "Clinical manifestations and diagnosis of Graves disease in children and adolescents", section on 'Diagnostic evaluation')
●Prolactin to assess for hyperprolactinemia (see "Causes of hyperprolactinemia")
●Testosterone and additional evaluation for polycystic ovary syndrome (PCOS) in females with signs of hyperandrogenism (hirsutism, acne, male pattern balding) (see "Diagnostic evaluation of polycystic ovary syndrome in adolescents")
Additional evaluation for hirsutism is discussed separately. (See "Evaluation of premenopausal women with hirsutism", section on 'Biochemical testing'.)
●Pelvic ultrasonography to look for ovarian pathology
If pathologic causes are ruled out, and the patient is not bothered by irregular menses, anovulatory bleeding may be managed expectantly for the first few years after menarche. Long-term monitoring of females with anovulatory uterine bleeding is discussed separately. (See "Abnormal uterine bleeding in adolescents: Management", section on 'Long-term monitoring'.)
Polycystic ovary syndrome — PCOS is another common cause of irregular bleeding in adolescents, though it also can be associated with other patterns of bleeding (eg, amenorrhea, infrequent bleeding, heavy bleeding) [3,11].
Clinical features of PCOS include physical signs of hyperandrogenism (hirsutism, acne, clitoromegaly) or laboratory signs of hyperandrogenism (elevated testosterone) in conjunction with menstrual irregularities and/or insulin resistance (eg, acanthosis nigricans) . Any of these findings may be the sole presenting feature of PCOS, but one feature is not sufficient to establish the diagnosis (table 6). (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents".)
The diagnosis of PCOS is based upon clinical and biochemical criteria. Other causes of hyperandrogenism and irregular menses must be excluded. The differential diagnosis and diagnostic evaluation of PCOS are discussed separately. (See "Definition, clinical features, and differential diagnosis of polycystic ovary syndrome in adolescents", section on 'Differential diagnosis' and "Diagnostic evaluation of polycystic ovary syndrome in adolescents".)
Other causes — Other hormonal causes of irregular bleeding in adolescents include :
●Hypothyroidism (may cause heavy menstrual bleeding as well as irregular bleeding) (see 'Causes of heavy menstrual bleeding' below)
●Hyperprolactinemia – Causes of hyperprolactinemia include pituitary tumors and certain medications (table 7) (may cause amenorrhea as well as irregular/less bleeding) (see "Causes of hyperprolactinemia" and "Clinical manifestations and evaluation of hyperprolactinemia", section on 'Menstrual cycle dysfunction')
●Hypothalamic dysfunction related to exercise, psychological stress, being underweight, acute weight loss, or obesity (may cause amenorrhea as well as irregular/less bleeding) (see "Evaluation and management of secondary amenorrhea")
Infections of the vulva, vagina, or cervix may cause intermenstrual bleeding that appears to be irregular. (See 'Causes of intermenstrual bleeding' below.)
Causes of heavy menstrual bleeding — In adolescents, heavy menstrual bleeding typically occurs at irregular intervals, indicating that it is anovulatory. (See 'Anovulatory uterine bleeding' above.)
Heavy menstrual bleeding that occurs at regular intervals or at the onset of menses often is related to a bleeding disorder [38-42]. Less commonly, heavy menstrual bleeding may be caused by systemic illness or structural lesions [39,43].
Bleeding disorders — We consider the possibility of a bleeding disorder (coagulation factor deficiency or inherited or acquired platelet disorder) in adolescents who present with first menses with extremely heavy flow, bleeding requiring blood transfusion or hospitalization, and patients with refractory heavy menstrual bleeding and concomitant anemia. In such patients, consultation with a hematologist is warranted [44,45].
In retrospective studies in adolescents hospitalized for heavy menstrual bleeding, the prevalence of bleeding disorders ranges from 5 to 28 percent [39-41,43,46]. In a series of 59 patients who were hospitalized with acute heavy menstrual bleeding and in whom genital tract pathology had been excluded, an underlying coagulopathy was identified in approximately 20 percent overall, 33 percent of those requiring transfusion, and 50 percent of those presenting at menarche .
In observational studies in adolescents who were evaluated in a hematology or multidisciplinary clinic for heavy menstrual bleeding, the prevalence of bleeding disorders ranges approximately 20 to 60 percent [42,47-51].
Bleeding disorders among adolescents with heavy menstrual bleeding include, but are not limited to [37-40,42,46,47,50]:
●von Willebrand disease (see "Clinical presentation and diagnosis of von Willebrand disease" and "von Willebrand disease (VWD): Gynecologic and obstetric considerations")
●Factor VII deficiency (see "Rare inherited coagulation disorders")
●Immune thrombocytopenia (see "Immune thrombocytopenia (ITP) in children: Clinical features and diagnosis")
●Platelet dysfunction (see "Congenital and acquired disorders of platelet function")
●Thrombocytopenia secondary to malignancy or treatment for malignancy (ie, chemotherapy or hematopoietic stem cell transplantation) (see "Causes of thrombocytopenia in children")
Among these, von Willebrand disease is most common; in a systematic review of 11 studies including 988 adult females presenting with heavy menstrual bleeding (not limited to adolescents), the prevalence of von Willebrand disease was 13 percent .
The minimum laboratory evaluation for bleeding disorder in adolescents with heavy menstrual bleeding should include (see "Approach to the child with bleeding symptoms", section on 'Initial laboratory evaluation') [12,44,53]:
●Complete blood count with platelets and examination of the peripheral blood smear and ferritin to detect anemia, iron deficiency without anemia , or thrombocytopenia
●Coagulation panel (activated partial thromboplastin time [aPTT]/partial thromboplastin time [PTT], prothrombin time [PT], and fibrinogen)
The evaluation generally also includes a von Willebrand panel [3,53,55,56]:
●Plasma von Willebrand factor (VWF) antigen
●Plasma VWF activity (ristocetin cofactor activity)
●Factor VIII activity
The von Willebrand panel should be obtained at the time of presentation or after exogenous estrogen has been discontinued for seven days. Exogenous estrogen may elevate VWF into the normal range .
Consultation with a hematologist is suggested if any abnormalities are detected on the von Willebrand panel. (See "Clinical presentation and diagnosis of von Willebrand disease".)
Other causes — Less common causes of heavy menstrual bleeding in adolescents include:
●Systemic illness that affects ovarian or liver function, causing abnormalities in ovulation (eg, diabetes mellitus) or coagulation (eg, systemic lupus erythematosus, renal failure, malignancy, myelodysplasia)
●Other endocrine disorders (eg, hypothyroidism, hyperthyroidism) may cause heavy menstrual bleeding as well as irregular bleeding
●Structural lesions (eg, polyps, uterine leiomyomas [fibroids])
●Medications (eg, anticoagulants, platelet inhibitors, nonsteroidal anti-inflammatory drugs including aspirin)
In adolescents with heavy menstrual bleeding in whom a bleeding disorder has been excluded, additional laboratory evaluation may include:
●Measurement of serum TSH to evaluate thyroid function (if not already performed)
●Evaluation for chronic disease, systemic disease, or medication-related bleeding as warranted by the history (table 2) and physical examination (table 4)
●Pelvic ultrasonography (if it has not already been performed) to assess structural causes, such as leiomyomas (fibroids), polyps, and/or ovarian tumors (see 'Pelvic ultrasonography' above)
Causes of intermenstrual bleeding
Hormonal contraception and intrauterine devices — Intermenstrual bleeding is a common side effect of oral contraceptives, depot medroxyprogesterone acetate, the contraceptive patch, the vaginal ring, the contraceptive implant, and intrauterine devices. Intermenstrual bleeding also may occur if hormonal contraception is not administered as prescribed. (See "Evaluation and management of unscheduled bleeding in individuals using hormonal contraception" and "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Unscheduled bleeding'.)
Before attributing intermenstrual bleeding to contraception, the possibility of pregnancy, cervicitis, or endometrial/cervical pathology must be considered and excluded by examination and/or appropriate laboratory tests.
Infection — Sexually transmitted infections (STI) may cause intermenstrual bleeding in sexually active adolescents and/or those who have been sexually abused or assaulted. Such patients who have acute vaginal bleeding unrelated to menses should be assessed for cervicitis and upper genital tract infection. The prevalence of Chlamydia trachomatis in females with AUB is underestimated . Routine screening for STI is recommended for sexually active adolescents with menstrual abnormalities. (See "Sexually transmitted infections: Issues specific to adolescents" and "Pelvic inflammatory disease: Clinical manifestations and diagnosis".)
Other causes — Extrauterine gynecologic causes of intermittent bleeding that may mimic intermenstrual uterine bleeding include:
●Cervical polyps (see "Benign cervical lesions and congenital anomalies of the cervix", section on 'Polyps')
●Cervical ectropion (eversion of the endocervix) (see "Benign cervical lesions and congenital anomalies of the cervix", section on 'Ectropion')
●Foreign bodies (retained tampons are most common among adolescents)
●Trauma (see "Evaluation of sexual abuse in children and adolescents" and "Evaluation and management of adult and adolescent sexual assault victims in the emergency department")
●Certain medications (eg, anticoagulants, valproic acid)
Less common causes of nonuterine genital tract bleeding in adolescents are discussed separately. (See "Causes of female genital tract bleeding".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)
●Basics topics (see "Patient education: Absent or irregular periods (The Basics)" and "Patient education: Heavy periods (The Basics)")
●Beyond the Basics topics (see "Patient education: Absent or irregular periods (Beyond the Basics)" and "Patient education: Abnormal uterine bleeding (Beyond the Basics)" and "Patient education: Heavy or prolonged menstrual bleeding (menorrhagia) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Terminology – Abnormal uterine bleeding (AUB) refers to menstrual bleeding that occurs outside the normal range and includes absence of menses, menses at irregular intervals, heavy menstrual flow, and intermenstrual bleeding. "Anovulatory uterine bleeding" is the preferred term for heavy noncyclic uterine bleeding unrelated to structural lesions of the uterus or systemic disease, the most common cause of AUB in adolescents. (See 'Terminology' above.)
●Causes – Adolescents with AUB typically present with a complaint of abnormal "vaginal bleeding." The uterus is the most likely source of vaginal bleeding (table 1). Anovulatory uterine bleeding related to immaturity of the hypothalamic-pituitary-ovarian axis is the most common cause of AUB in nonpregnant adolescents in the first year or two after menarche. (See 'Causes of vaginal bleeding in adolescents' above.)
●Triage – Initial triage of the adolescent with suspected abnormal uterine bleeding includes assessment of hemodynamic stability and pregnancy status. (See 'Triage' above.)
•Patients who are hemodynamically unstable (eg, tachycardic, hypotensive, orthostatic) should be referred/transported to the emergency department for stabilization and hospitalization before proceeding with additional evaluation.
•Urine pregnancy test is essential, regardless of the stated sexual history. Pregnancy and pregnancy-related problems commonly cause uterine bleeding in adolescents and may be life-threatening (eg, ectopic pregnancy, pregnancy loss). (See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)
●Approach to diagnosis – In the nonpregnant adolescent with AUB, the history (table 2), examination (table 4), and initial laboratory evaluation focus on clinical features associated with specific causes and identification of the predominant bleeding pattern, which determines additional evaluation (table 5).
•Amenorrhea – Pregnancy is the most common cause of amenorrhea in reproductive-age females. The approach to amenorrhea is discussed separately. (See "Evaluation and management of primary amenorrhea" and "Evaluation and management of secondary amenorrhea".)
•Irregular bleeding – Immaturity of the hypothalamic-pituitary-ovarian axis with anovulatory cycles is the most common cause of irregular bleeding in nonpregnant adolescents during the first one to two years after menarche. Other causes include polycystic ovary syndrome, hyperprolactinemia, and hypothalamic dysfunction related to exercise, stress, or changes in body weight. (See 'Causes of irregular bleeding' above.)
•Prolonged and/or heavy menstrual bleeding – Bleeding disorders (eg, von Willebrand disease) are a common cause of prolonged and/or heavy menstrual bleeding in nonpregnant adolescents with regular menses. Bleeding disorders also should be considered in adolescents with AUB who present with first menses with extremely heavy flow, bleeding requiring blood transfusion, and refractory heavy menstrual bleeding with concomitant anemia. (See 'Bleeding disorders' above.)
•Intermenstrual bleeding – Causes of intermenstrual bleeding in adolescents include use of hormonal contraception or intrauterine devices, sexually transmitted infections, and extrauterine causes of intermittent bleeding that mimic intermenstrual uterine bleeding. (See 'Causes of intermenstrual bleeding' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate, Inc. acknowledge Dr. Robert Zurawin, MD, who contributed to an earlier version of this topic review.
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